Gene Therapy for Inherited Retinal Dystrophy (Luxturna®)
A gene therapy called Luxturna® is a new breakthrough in care for individuals with an inherited retinal dystrophy due to two mutations in the gene RPE65. It is offered by the Division of Ophthalmology at Children’s Hospital of Philadelphia (CHOP) to children who meet certain criteria.
What are inherited retinal dystrophies?
Retinal dystrophies are a group of eye disorders characterized by the degeneration of different parts of the retina. They are genetically heterogeneous, meaning mutations in many different genes may be responsible. Determining the specific gene mutation(s) is critical to understand the range of symptoms and treatment possibilities.
What type of gene therapy is available for retinal dystrophies?
In 2017, a gene therapy called Luxturna was approved by the U.S. Food and Drug Administration for use in children and adults with retinal disease due to two mutations in the gene RPE65. As mentioned, there are many genes that can cause retinal dystrophies, but at this time treatment is only clinically available for RPE65-related disease.
Who is a candidate for gene therapy?
Children (over 12 months of age) and adults who have genetically confirmed mutations in both copies of the RPE65 gene may be candidates for gene therapy. Patients must undergo a complete clinical evaluation and testing to determine if there are enough remaining cells in the retina to receive the treatment.
How does gene therapy for inherited retinal dystrophies work?
Luxturna provides a working copy of the RPE65 gene to the retinal cells of the eye. This allows cells to make the RPE65 protein, which allows the visual cycle to continue and for light to be converted to electrical signals to be interpreted by the brain.
-
Narrator: Our team at Children's Hospital of Philadelphia wants to help you understand in vivo gene therapy. But before we can get into what in vivo means, we should start by explaining what is gene therapy? Gene therapy is a way to treat or prevent disease by using genetic material like DNA. First, the basics.
Our bodies are made up of cells. And inside each cell is its DNA. DNA is divided into short sections called genes. Genes act as instruction manuals, telling our cells how to make proteins. Proteins are necessary for our bodies to function. Proteins do important work like helping us digest food and helping our blood clot when we get a cut.
But sometimes, a gene's instructions for making a protein are not correct. This can cause changes in how a protein works. These incorrect instructions can result in a genetic disease. Gene therapy can deliver new instructions to the body to make proteins that function correctly.
Hannah: I was going blind. After I received a healthy gene to replace the bad gene in my eyes, I was able to see so much better.
Narrator: How does gene therapy work? There are two types of gene therapy. Ex vivo and in vivo. Ex vivo means outside the body. When a child receives ex vivo gene therapy, it means their cells are removed from their body, treated with gene therapy, and then put back into their body. In vivo means inside the body.
Let's talk more about how in vivo gene therapy works. When a child receives in vivo gene therapy, we use something called a vector, which acts like a delivery truck. Vectors with the new or corrected gene can get into the body through an iv, or doctors can put them in a specific spot, like the eye. The vector then travels to the cells where the corrected gene is needed.
With the help of the new gene, the cells start making the proper kind of protein. One condition that can be treated with an in vivo gene therapy, is spinal muscular atrophy, which is a nerve disease that used to be fatal for children with a severe type. Children with a disease now can receive an in vivo gene therapy that stops the progression of the condition.
William: Because of spinal muscular atrophy, I couldn't even roll over after gene therapy. I can now stand and take steps.
Narrator: Gene therapy is changing and saving children's lives and CHOP has been at the forefront of gene therapy breakthroughs from the start. CHOP was the first in the world to use in vivo gene therapy delivered into the bloodstream, which is the most commonly used method today.
And we've pioneered many other groundbreaking discoveries. Our determined researchers are exploring the use of in vivo gene therapy for all kinds of diseases so that more children worldwide will have bright futures.
How is Luxturna given?
Luxturna is delivered as a subretinal injection. The procedure takes place in the operating room while the patient is under anesthesia. Patients undergo two separate procedures (one for each eye), at least one week apart. They are treated with a corticosteroid before and after each surgery.
What kind of follow-up is needed?
Luxturna is designed as a one-time therapy. Following surgery, the eye will be covered with a patch for 24-48 hours. Patients will have frequent follow-up visits with the surgeon and retinal specialist in the initial postoperative period. Patients will not be able to travel by plane right away. After cleared to travel home, patients should have follow-up visits with a retinal specialist at least once a year.
Why choose CHOP for RPE65 gene therapy?
CHOP is a designated Ocular Gene Therapy Treatment Center. CHOP co-sponsored and was the primary site of the gene therapy clinical trial, and gained early experience administering the treatment. At CHOP, your child has access to a dedicated care team, including ophthalmologists, ophthalmic geneticists, a retinal surgeon and a genetic counselor – all of whom have experience diagnosing and caring for children with inherited retinal conditions and their families. Our multidisciplinary team provides the latest treatment breakthroughs and offers exceptional support for families before, during and after treatment.
Required reports for evaluation and referral:
- Detailed medical summary, including ophthalmology reports
- Clinical diagnosis of retinal disease
- Genetic test results (patient and parent test results showing biparentally inherited RPE65 mutations)